The long term goals of this proposal are to examine the molecular and cellular bases of very early events in inner ear development in order to understand the mechanisms that give rise to congenital deafness. The specific aims of this proposal focus on examining the importance of the developmentally regulated transcription factor, Pax-2, one of the earliest genes expressed in the otic placode and its potential downstream target K-cadherin (cCad6B in the chick). The first specific aim is designed to set up a blueprint of the mRNA and protein expression patterns of Pax-2 and K-cadherin from otic placode invagination (stage 8) through development of the three dimensional inner ear structure (stage 38). The second and third specific aims further examine the correlation between Pax-2 and K-cadherin expression. In both aims the localization of Pax2 and K-cadherin mRNA and protein will be examined in otocysts which have been either surgically manipulated (in specific aim 2) or exposed to factors causing overexpression or downregulation of the Pax-2 gene product (in specific aim 3). Both these sets of experiments will be performed in ovo and are expected to reveal the important interactions between the cellular environment and Pax-2 expression in addition to looking at the correlation between Pax-2 and K-cadherin expression. The fourth specific aim examines the importance of K-cadherin function for formation of the statoacoustic ganglion. These experiments involve functional blocking of K-cadherin activity and will be performed both in vitro, on organ cultures, and in vivo.